Mechanism of anion selectivity and stoichiometry of the Na +/I - symporter (NIS)

Monika Paroder-Belenitsky, Matthew J. Maestas, Orsolya Dohán, Juan Pablo Nicola, Andrea Reyna-Neyra, Antonia Follenzi, Ekaterina Dadachova, Sepehr Eskandari, Mario L Amzel, Nancy Carrasco

Research output: Contribution to journalArticle

Abstract

I - uptake in the thyroid, the first step in thyroid hormone biosynthesis, is mediated by the Na +/I - symporter (NIS) with an electrogenic 2Na + : 1I - stoichiometry. We have obtained mechanistic information on NIS by characterizing the congenital I - transport defect-causing NIS mutant G93R. This mutant is targeted to the plasma membrane but is inactive. Substitutions at position 93 show that the longer the side chain of the neutral residue at this position, the higher the K m for the anion substrates. Unlike WT NIS, which mediates symport of Na + and the environmental pollutant perchlorate electroneutrally, G93T/N/Q/E/D NIS, strikingly, do it electrogenically with a 2:1 stoichiometry. Furthermore, G93E/Q NIS discriminate between anion substrates, a discovery with potential clinical relevance. A 3D homology model of NIS based on the structure of the bacterial Na +/galactose transporter identifies G93 as a critical player in the mechanism of the transporter: the changes from an outwardly to an inwardly open conformation during the transport cycle use G93 as a pivot.

Original languageEnglish (US)
Pages (from-to)17933-17938
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number44
DOIs
StatePublished - Nov 1 2011

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Symporters
Anions
Bacterial Structures
Environmental Pollutants
Ion Transport
Galactose
Thyroid Hormones
Thyroid Gland
Cell Membrane

Keywords

  • Homology modeling
  • Iodide transport defect
  • Radioiodide therapy
  • Sodium solute cotransporter family

ASJC Scopus subject areas

  • General

Cite this

Paroder-Belenitsky, M., Maestas, M. J., Dohán, O., Nicola, J. P., Reyna-Neyra, A., Follenzi, A., ... Carrasco, N. (2011). Mechanism of anion selectivity and stoichiometry of the Na +/I - symporter (NIS). Proceedings of the National Academy of Sciences of the United States of America, 108(44), 17933-17938. https://doi.org/10.1073/pnas.1108278108

Mechanism of anion selectivity and stoichiometry of the Na +/I - symporter (NIS). / Paroder-Belenitsky, Monika; Maestas, Matthew J.; Dohán, Orsolya; Nicola, Juan Pablo; Reyna-Neyra, Andrea; Follenzi, Antonia; Dadachova, Ekaterina; Eskandari, Sepehr; Amzel, Mario L; Carrasco, Nancy.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 44, 01.11.2011, p. 17933-17938.

Research output: Contribution to journalArticle

Paroder-Belenitsky, M, Maestas, MJ, Dohán, O, Nicola, JP, Reyna-Neyra, A, Follenzi, A, Dadachova, E, Eskandari, S, Amzel, ML & Carrasco, N 2011, 'Mechanism of anion selectivity and stoichiometry of the Na +/I - symporter (NIS)', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 44, pp. 17933-17938. https://doi.org/10.1073/pnas.1108278108
Paroder-Belenitsky, Monika ; Maestas, Matthew J. ; Dohán, Orsolya ; Nicola, Juan Pablo ; Reyna-Neyra, Andrea ; Follenzi, Antonia ; Dadachova, Ekaterina ; Eskandari, Sepehr ; Amzel, Mario L ; Carrasco, Nancy. / Mechanism of anion selectivity and stoichiometry of the Na +/I - symporter (NIS). In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 44. pp. 17933-17938.
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